Macromolecular Protein Complexes

Victor M. Bolanos-Garcia

J. Robin Harris, Jon Marles-Wright

Mistakes in the process of cell division can lead to the loss, gain or rearrangement of chromosomes. Significant chromosomal abnormalities are usually lethal to the cells and cause spontaneous miscarriages. However, in some cases, defects in the spindle assembly checkpoint lead to severe diseases, such as cancer and birth and development defects, including Down's syndrome. The timely and accurate control of chromosome segregation in mitosis relies on the spindle assembly checkpoint (SAC), an evolutionary conserved, self-regulated signalling system present in higher organisms. The spindle assembly checkpoint is orchestrated by dynamic interactions between spindle microtubules and the kinetochore , a multiprotein complex that constitutes the site for attachment of chromosomes to microtubule polymers to pull sister chromatids apart during cell division. This chapter discusses the current molecular understanding of the essential, highly dynamic molecular interactions underpinning spindle assembly checkpoint signalling and how the complex choreography of interactions can be coordinated in time and space to finely regulate the process. The potential of targeting this signalling pathway to interfere with the abnormal segregation of chromosomes, which occurs in diverse malignancies and the new opportunities that recent technological developments are opening up for a deeper understanding of the spindle assembly checkpoint are also discussed.